PL53336B1 - - Google Patents

Description

Priority: Published: 10.Y.1967 53336 KI. 12 o, 11 MKP C 07 c UKD AlAt. Co-authors of the invention: Wladyslaw Brud, MSc, Jerzy Lange, PhD, Assoc. dr Barbara Serafinowa, prof. Tadeusz Urbanski, PhD. Patent proprietor: Lódzkie Zaklady Farmaceutyczne "Polfa" Przedsiebiorstwo Panstwowe, Lodz (Poland) The method of producing trinitriles, beta-substituted tricarballylic acid derivatives. wherein Ar is any aromatic substituent, such as phenylic, m-bromophenyl, p-methylphenyl or heterocyclic aromatic substituents, such as pyridyl, thienyl, or unsaturated such as cyclohexenyl, or any other substituent capable of activating Hydrogen atoms bound to the adjacent carbon atom. These compounds are intermediates for the preparation of tricarboxylic acids and their derivatives, which can be used in the production of a number of drugs in the pharmaceutical industry. It is known to obtain compounds of formula 1 by reactions of acetonitrile derivatives with chlorine - co-acetonitrile in an anhydrous solution Organic solvents, such as benzene, toluene or ether, against condensing agents, such as sodium, sodium amide, sodium hydride or sodium alkoxide, which bind the hydrogen halide produced during the reaction. Carrying out the cyanomethylation process under the conditions of the absolute anhydrousness of the reaction environment and the use of very dangerous substances, such as sodium, sodium amide or sodium hydride, presents many inconveniences. It has been found that these inconveniences in the production of trinitriles of the general formula I can be If not, if the methylene-active acetonitrile derivatives of formula II, in which Ar is as defined above, will be reacted with haloacetonitrile of formula III, in which X is a halogen atom, in the presence of alkali metal hydroxides in the environment in an aqueous or organic solvent environment, or in a mixture of organic solvents with water in the presence of a quaternary ammonium salt or base. The quaternary ammonium salt or base acts as a catalyst for the reaction and is used in amounts of less than 0.1 mole per 1 mole of starting nitrile. May also be used as reaction catalyst in place of quaternary of these ammonium compounds are the tertiary amines which form the corresponding quaternary ammonium compounds with halogen acetonitrile. According to the invention, the cyano-methylation process is carried out at temperatures ranging from 10 to 50 ° for several minutes to about 2 hours, using two moles of haloacetonitrile per mole of acetonitrile derivative. The tritrile obtained by the method of the invention can be easily The compounds obtained by the process of the invention have two nitrile groups of primary character and one nitrile group of tertiary nature. Therefore, the two types of nitrile groups behave differently in the hydrolysis reaction process. Depending on the hydrolysis conditions of the obtained trinitriles, they can be converted into the corresponding tricarboxylic acids, cyano acids, amido acids, cyanamides, cyanoesters, cyanoimides and other compounds, some of which still have the possibility of positional isomerism. The embodiments of the invention y explain the essence of the invention, without limiting its scope. * '"Example I. 40 g of p-fluorobenzyl cyanide, 40 g of trillium chloroacetonium and 0.06 g of triethylamine are mixed and 98 ml 50 ° are added The reaction mass is stirred for 20 minutes at 25 ° -40 °, after which 700 ml of water are added, extracted with ether, the ethereal layer is separated, washed with water and dried. The solvent is stripped from the dried ethereal solution, and the residue is crystallized from butyl alcohol to give 44 g of (p-fluorophenyl) -carballyl tritrile, mp 91-93 °, which is 71% of this yield. theoretical Example II. 30 g of p-bromobenzyl cyanide, 36.7 g of bromoacetonitrile and 0.34 g of triethylbenzyl ammonium chloride, are mixed with 40 ml of a 50% aqueous sodium hydroxide solution at room temperature with continuous stirring. The reaction mass is then diluted with water and cooled to a temperature of 2-3 °, while a crystalline precipitate is separated, which is filtered off and recrystallized from water. After drying, 34 g of O- (p-bromophenyl) tricarbolic acid trinitrile, mp 106-108 °, are obtained, which is 81% of theory. 10 15 20 25 85 PL

Claims (1)

Claims 1. Process for the preparation of trinitriles, beta-substituted tricarballylic acid derivatives of the general formula I, in which Ar is an aromatic substituent such as phenyl, m-bromophenyl, p-methylphenyl or heterocyclic aromatic substituents such as pyridyl. thienyl or unsaturated, such as cyclohexenyl or any other substituent which has the ability to activate hydrogen atoms bound to the adjacent carbon atom by reaction of acetonitrile derivatives with chloroacetonitrile in the presence of condensing agents in an organic solvent environment characterized by methylene group acetonitriles of formula II, in which Ar is as defined above, are reacted with halogen-acetonitrile of formula III, in which X is a halogen atom, in the presence of alkali metal hydroxides as condensing agents in an aqueous environment or in an environment of organic solvents or in the environment of organic mixtures other solvents and water, in the presence of quaternary ammonium compounds in an amount less than 0.1 mole per 1 mole of alkylated nitrile as reaction catalysts at a temperature of 10 to 50 ° for several minutes to about two hours, using 1 mole of the acetonitrile derivative, two moles of haloacetonitrile, then the obtained product is isolated in a known manner. The method according to p. The process of claim 1, wherein the catalyst is a tertiary ammonium which, under the reaction conditions, forms an appropriate quaternary ammonium compound with cyanomethylating halogen acetonitrile. CHi-CN Ar-C-CN CHz-CN Formula and Ar-CHz-CN Formula 2 X-CHz-CN Formula 5 WDA-l. Order 425/67. Nakl. 310 copies PL